ArticleNucleic acids research2020
Developing an endogenous quorum-sensing based CRISPRi circuit for autonomous and tunable dynamic regulation of multiple targets in Streptomyces.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 78 citations in OpenAlex.
- Enhanced spinosad production inSynthetic and systems biotechnology · 2026Article
- Cross-Strain Transferability of CRISPRi Systems and Design Rules from Laboratory to ClinicalACS synthetic biology · 2026Article
- Cross-strain transferability of CRISPRi systems and design rules from laboratory to clinicalbioRxiv : the preprint server for biology · 2026Article
- A noncanonical transcriptional regulation in natural product biosynthesis.Nucleic acids research · 2026Article
- Integrated multi-omics and genome mining strategies for activating cryptic polyketide biosynthetic gene clusters inFrontiers in microbiology · 2026Review
- The regulatory role of histidine kinase in modulating nucleoside metabolites inFrontiers in microbiology · 2026Article
- A quorum sensing-controlled type I CRISPRi toolkit for dynamically regulating metabolic flux.Nucleic acids research · 2025Article
- CRISPRi-mediated multigene downregulating redirects the metabolic flux to spinosad biosynthesis inSynthetic and systems biotechnology · 2025Article
- The Cytotoxic Activity of Secondary Metabolites from Marine-DerivedMarine drugs · 2025Review
- Identification of a novel butenolide signal system to regulate high production of tylosin in Streptomyces fradiae.Applied microbiology and biotechnology · 2025Article
- Engineered CRISPR-Cas9 for Streptomyces sp. genome editing to improve specialized metabolite production.Nature communications · 2025Article
- Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad inSynthetic and systems biotechnology · 2024Article
- Repurposing endogenous type I-E CRISPR-Cas systems for natural product discovery in Streptomyces.Nature communications · 2024Article
- AI-Assisted Rational Design and Activity Prediction of Biological Elements for Optimizing Transcription-Factor-Based Biosensors.Molecules (Basel, Switzerland) · 2024Review
- Investigating and Engineering an 1,2-Propanediol-Responsive Transcription Factor-Based Biosensor.ACS synthetic biology · 2024Article
- Tunable translation-level CRISPR interference by dCas13 and engineered gRNA in bacteria.Nature communications · 2024Article
- Enhancement of acyl-CoA precursor supply for increased avermectin B1a production by engineering meilingmycin polyketide synthase and key primary metabolic pathway genes.Microbial biotechnology · 2024Article
- An inducible CRISPRi circuit for tunable dynamic regulation of gene expression in Saccharopolyspora erythraea.Biotechnology letters · 2024Article
- A toolbox for genetic manipulation in intestinalSynthetic and systems biotechnology · 2024Article
- CRISPR-aided genome engineering for secondary metabolite biosynthesis in Streptomyces.Journal of industrial microbiology & biotechnology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Quorum-sensing (QS) mediated dynamic regulation has emerged as an effective strategy for optimizing product titers in microbes. However, these QS-based circuits are often created on heterologous systems and require careful tuning via a tedious testing/optimization process. This hampers their application in industrial microbes. Here, we design a novel QS circuit by directly integrating an endogenous QS system with CRISPRi (named EQCi) in the industrial rapamycin-producing strain Streptomyces rapamycinicus. EQCi combines the advantages of both the QS system and CRISPRi to enable tunable, autonomous, and dynamic regulation of multiple targets simultaneously. Using EQCi, we separately downregulate three key nodes in essential pathways to divert metabolic flux towards rapamycin biosynthesis and significantly increase its titers. Further application of EQCi to simultaneously regulate these three key nodes with fine-tuned repression strength boosts the rapamycin titer by ∼660%, achieving the highest reported titer (1836 ± 191 mg/l). Notably, compared to static engineering strategies, which result in growth arrest and suboptimal rapamycin titers, EQCi-based regulation substantially promotes rapamycin titers without affecting cell growth, indicating that it can achieve a trade-off between essential pathways and product synthesis. Collectively, this study provides a convenient and effective strategy for strain improvement and shows potential for application in other industrial microorganisms.
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